Human episodic neurological diseases have a broad range of symptoms, including migraine, ataxia, dyskinesia, and epilepsy. That many are linked to ion channel mutations and are characterized by attacks that are triggered by similar precipitants, suggests similar mechanisms of pathogenesis. However, these mechanisms are not understood. The tottering mouse syndrome is a useful model of human episodic neurological disease, as it results from a calcium channel mutation, and is characterized by attacks of dyskinesia that are triggered by clinically relevant precipitants. Moreover, tottering attacks are alleviated by treatments that are also effective in patients. Discerning the mechanisms of episodic neurological dysfunction in the tottering syndrome will likely yield insights regarding the pathogenesis of the human episodic channelopathies. Preliminary studies suggest that altered handling of store-operated calcium contribute to tottering attacks. We hypothesize that release of store-operated calcium in tottering induces attacks by causing aberrant cerebellar output. The specific aims of this proposal are 1) to assess the role of calcium signaling in tottering attacks 2) to characterize cerebellar signaling during tottering attacks. [unreadable] [unreadable] [unreadable]